1-214403170-C-T

Position:

• chr1-214403170-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005401.5(PTPN14):​c.511-217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,106 control chromosomes in the GnomAD database, including 2,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.19 (2990 hom., cov: 32)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.120

Genes affected

PTPN14 (HGNC:9647): (protein tyrosine phosphatase non-receptor type 14) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-214403170-C-T is Benign according to our data. Variant chr1-214403170-C-T is described in ClinVar as [Benign]. Clinvar id is 1280145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.511-217G>A		intron_variant		ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.511-217G>A		intron_variant		1	NM_005401.5	ENSP00000355923.4
PTPN14	ENST00000543945.5	c.511-217G>A		intron_variant		5		ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29195 AN: 151988 Hom.: 2988 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29218 AN: 152106 Hom.: 2990 Cov.: 32 AF XY: 0.191 AC XY: 14242 AN XY: 74388

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.224

Alfa AF: 0.187 Hom.: 2906

Bravo AF: 0.208

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6657749; hg19: chr1-214576513;